9-Deoxy-6,9α-epoxymethano-pg C-1 amides

ABSTRACT

Processes for preparing prostacyclin analogs which are 9-deoxy-6,9-epoxymethano derivatives of prostaglandin F 1 α -type compounds, illustrated, for example, by a compound of the formula ##STR1## wherein ˜indicates alpha or beta configuration; including the products and intermediates produced therein, said products having pharmacological utility.

The present application is a divisional application of Ser. No. 788,145, filed Apr. 19, 1977, now issued as U.S. Pat. No. 4,130,569, on Dec. 19, 1978.

The present invention relates to prostaglandin analogs for which the essential material constituting a disclosure therefor is incorporated by reference here from U.S. Pat. No. 4,130,569. 

I claim:
 1. A cyclic ether of the formula ##STR2## wherein L is (1) a valence bond, (2) --(CH₂)_(d) --wherein d is one to 5 inclusive, (3) --(CH₂)_(t) --CF₂ --wherein t is 2, 3, or 4, (4) --CH₂ --CH═CH--A-- wherein A is a valence bond or --(CH₂)_(h) -- wherein h is one, 2, or 3, or (5) --CH₂ --O--CH₂ --Y-- wherein Y is a valence bond or --(CH₂)_(k) -- wherein k is one or 2; wherein Q₂ is ##STR3## wherein R₃ is hydrogen or alkyl of one to 4 carbon atoms, inclusive; wherein R₁₈ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, benzyl, or phenyl, the two R₁₈ 's being the same or different;wherein R₂₁ is ##STR4## wherein R₂₅ is ##STR5## wherein C_(g) H₂.sbsb.g is alkylene of one to 9 carbon atoms, inclusive, with one to 5 carbon atoms, inclusive, in the chain between --CR₅ R₆ -- and terminal methyl, wherein R₅ and R₆ are hydrogen, alkyl of one to 4 carbon atoms, inclusive, or fluoro, being the same or different, with the proviso that one of R₅ and R₆ is fluoro only when the other is hydrogen or fluoro; ##STR6## wherein R₅ and R₆ are as defined above with the proviso that neither R₅ nor R₆ is fluoro when Z is oxa (--O--); wherein Z represents an oxa atom (--O--) or C_(j) H₂.sbsb.j wherein C_(j) H₂.sbsb.j is a valence bond or alkylene of one to 9 carbon atoms, inclusive, substituted with zero, one, or 2 fluoro, with one to 6 carbon atoms, inclusive between --CR₅ R₆ -- and the phenyl ring; wherein T is alkyl of one to 4 carbon atoms, inclusive, fluoro, chloro, trifluoromethyl, or --OR₇ wherein R₇ is alkyl of one to 4 carbon atoms, inclusive, and s is zero, one, 2, or 3, with the proviso that not more than two T's are other than alkyl and when s is 2 or 3 the T's are either the same or different; or ##STR7## wherein X is cis-- or trans--CH═CH--, --C.tbd.C--, or --CH₂ CH₂ --; and wherein the wavy line (˜) indicates attachment in cis or trans configuration.
 2. A compound according to claim 1 wherein X is trans--CH═CH--.
 3. A compound according to claim 2 wherein Q₂ is ##STR8## wherein R₃ is hydrogen, methyl, or ethyl.
 4. A compound according to claim 3 wherein R₂₁ is ##STR9##
 5. A compound according to claim 4 wherein L is --(CH₂)_(d) -- wherein d is one to 5 inclusive.
 6. A compound according to claim 5 wherein R₂₅ is ##STR10##
 7. A compound according to claim 6 wherein ##STR11## is n-pentyl.
 8. 9-Deoxy-6ξ,9α-epoxymethano-PGF₁, amide, less polar isomer and more polar isomer, compounds according to claim
 7. 9. A compound according to claim 5 wherein R₂₅ is ##STR12##
 10. A compound according to claim 9 wherein ##STR13##
 11. A compound according to claim 9 wherein ##STR14##
 12. A compound according to claim 4 wherein L is --(CH₂)_(t) --CF₂ -- wherein t is 2, 3, or
 4. 13. A compound according to claim 3 wherein R₂₁ is ##STR15## 